Dataset Information

High Plasma Soluble CD163 During Infancy Is a Marker for Neurocognitive Outcomes in Early-Treated HIV-Infected Children.

ABSTRACT: BACKGROUND:Monocyte activation may contribute to neuronal injury in aviremic HIV-infected adults; data are lacking in children. We examined the relation between monocyte activation markers and early and long-term neurodevelopmental outcomes in early-treated HIV-infected children. SETTING:Prospective study of infant and child neurodevelopmental outcomes nested within a randomized clinical trial (NCT00428116) and extended cohort study in Kenya. METHODS:HIV-infected infants (N = 67) initiated antiretroviral therapy (ART) at age <5 months. Plasma soluble (s) CD163 (sCD163), sCD14, and neopterin were measured before ART (entry) and 6 months later. Milestone attainment was ascertained monthly during 24 months, and neuropsychological tests were performed at 5.8-8.2 years after initiation of ART (N = 27). The relationship between neurodevelopment and sCD163, sCD14, and neopterin at entry and 6 months after ART was assessed using Cox proportional hazards models and linear regression. RESULTS:Infants with high entry sCD163 had unexpected earlier attainment of supported sitting (5 vs 6 months; P = 0.006) and supported walking (10 vs 12 months; P = 0.02) with trends in adjusted analysis. Infants with high 6-month post-ART sCD163 attained speech later (17 vs 15 months; P = 0.006; adjusted hazard ratio, 0.47; P = 0.02), threw toys later (18 vs 17 months; P = 0.01; adjusted hazard ratio, 0.53; P = 0.04), and at median 6.8 years after ART, had worse neuropsychological test scores (adj. mean Z-score differences, cognition, -0.42; P = 0.07; short-term memory, -0.52; P = 0.08; nonverbal test performance, -0.39, P = 0.05). CONCLUSIONS:Before ART, monocyte activation may reflect transient neuroprotective mechanisms in infants. After ART and viral suppression, monocyte activation may predict worse short- and long-term neurodevelopment outcomes.

SUBMITTER: Benki-Nugent SF

PROVIDER: S-EPMC6889809 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

High Plasma Soluble CD163 During Infancy Is a Marker for Neurocognitive Outcomes in Early-Treated HIV-Infected Children.

Benki-Nugent Sarah F SF Martopullo Ira I Laboso Tony T Tamasha Nancy N Wamalwa Dalton C DC Tapia Kenneth K Langat Agnes A Maleche-Obimbo Elizabeth E Marra Christina M CM Bangirana Paul P Boivin Michael J MJ John-Stewart Grace C GC

Journal of acquired immune deficiency syndromes (1999) 20190501 1

<h4>Background</h4>Monocyte activation may contribute to neuronal injury in aviremic HIV-infected adults; data are lacking in children. We examined the relation between monocyte activation markers and early and long-term neurodevelopmental outcomes in early-treated HIV-infected children.<h4>Setting</h4>Prospective study of infant and child neurodevelopmental outcomes nested within a randomized clinical trial (NCT00428116) and extended cohort study in Kenya.<h4>Methods</h4>HIV-infected infants (N ...[more]

PMID: 30768490

Similar Datasets

Project description:BackgroundMonocytes play a central role in HIV neuropathogenesis, but there are limited data on monocyte subsets and markers of monocyte activation in perinatally HIV-infected children.ObjectiveTo determine the relationship between monocyte subsets, the sCD163 monocyte activation marker, and neuropsychological performance among perinatally HIV-infected children initiating antiretroviral therapy (ART).MethodsART-naïve children from the PREDICT study were categorised into two groups: those on ART for ≥24 weeks (ART group, n =201) and those untreated (no ART group, n =79). This analysis used data from the baseline and week 144 including sCD163 and frequencies of activated monocytes (CD14+/CD16+/HLA-DR+), perivascular monocytes (CD14+/CD16+/CD163+ and CD14low/CD16+/CD163+), and neuropsychological testing scores: Verbal and Performance Intelligence Quotient (VIQ and PIQ), Beery Visuomotor Integration (VMI) and Children's Color Trails 2 (CT2).ResultsBaseline demographic and HIV disease parameters were similar between groups. The median age was 6 years, CD4 was 20% (620 cells/mm3), and HIV RNA was 4.8 log10. By week 144, the ART vs the no ART group had significantly higher CD4 (938 vs 552 cells/mm3) and lower HIV RNA (1.6 vs 4.38 log10 copies/mL, P <0.05). sCD163 declined in the ART vs no ART group (median changes -2533 vs -159 ng/mL, P <0.0001). Frequencies of all monocyte subsets declined in the treated but not the untreated group (P <0.05). Higher CD14+/CD16+/HLA-DR+ percentage was associated with higher VIQ, Beery VMI and CT2 scores. Higher percentages of CD14+/CD16+/CD163+ and CD14low/CD16+/CD163+ were associated with higher CT2 and VIQ, respectively.ConclusionART significantly reduced sCD163 levels and frequencies of activated and perivascular monocytes. Higher frequencies of these cells correlated with better neuropsychological performance suggesting a protective role of monocyte-macrophage immune activation in perinatal HIV infection in terms of neuropsychological function.

Project description:Background HIV-associated neurocognitive disorders (HAND) are one of the HIV-associated comorbidities affecting 20–50% of the people with HIV (PWH) infection. We found that the soluble insulin receptor (sIR) levels in plasma and cerebrospinal fluid (CSF) were significantly higher in HIV-infected women. The mechanism of sIR release into the plasma remains unknown, but the detection of the sIR in exosomes may uncover novel mechanisms of sIR secretion from HIV-infected cells and its contribution to HIV disease progression and HAND development. Quantification of sIR in urine may represent a less invasive and more accessible diagnostic tool. Our objective was to quantify sIR levels in plasma, plasma-derived exosomes, and urine, and evaluate their association with HAND and renal function. Methods We measured full-length sIR in the plasma and urine of 38 controls and 76 HIV-infected women by ELISA, and sIR, HIV-1 Tat, and reactive oxygen species (ROS) in exosomes by flow cytometry. Results Plasma and exosomes with sIR were significantly higher in HIV-infected women when compared with controls and HAND. Exosomal sIR positively correlated with exosomal ROS and exosomal HIV-1 Tat in HIV-infected women. Exosomal ROS was significantly higher in HIV-infected women with more symptomatic cognitive impairment. Plasma-derived exosomes exhibited significantly higher levels of astrocyte (GFAP) and neuronal (L1CAM) markers in HIV-infected women, confirming the presence of circulating CNS-derived exosomes in the blood of HIV-infected women. Urine sIR positively correlated with eGFR in controls, but not in HIV-infected women, regardless there was no significant difference in renal function as determined by the estimated glomerular filtration rate (eGFR, p = 0.762). In HIV-infected women, higher plasma sIR correlated with lower urine sIR that could suggest sIR retention in blood or decreased renal filtration. Discussion Higher plasma sIR levels and their correlation with ROS in plasma-derived exosomes with HAND suggest a combined role of metabolic disturbances, oxidative stress, exosome release, and cognitive decline. Communication between CNS and periphery is compromised in PWH, thus plasma-derived exosomes may shed light on disrupted cellular mechanisms in the brain of PWH. High plasma and low urine sIR levels could suggest sIR retention in blood or decreased renal filtration.

Dataset Information

High Plasma Soluble CD163 During Infancy Is a Marker for Neurocognitive Outcomes in Early-Treated HIV-Infected Children.

Publications

High Plasma Soluble CD163 During Infancy Is a Marker for Neurocognitive Outcomes in Early-Treated HIV-Infected Children.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets